Matches in SemOpenAlex for { <https://semopenalex.org/work/W3022865720> ?p ?o ?g. }
- W3022865720 abstract "Abstract Developing neurons undergo dramatic morphological changes to appropriately migrate and extend axons to make synaptic connections. The microtubule cytoskeleton, made of α/β-tubulin dimers, drives neurite outgrowth, promotes neuronal growth cone responses, and facilitates intracellular transport of critical cargoes during neurodevelopment. TUBA1A constitutes the majority of α-tubulin in the developing brain and mutations to TUBA1A in humans cause severe brain malformations accompanied by varying neurological defects, collectively termed tubulinopathies. Studies of TUBA1A function in vivo have been limited by the presence of multiple genes encoding highly similar tubulin proteins, which prevents TUBA1A-specific antibody generation and makes genetic manipulation challenging. Here we present a novel tagging method for studying and manipulating TUBA1A in cells without impairing tubulin function. Using this tool, we show that a TUBA1A loss-of-function mutation TUBA1A N102D ( TUBA1A ND ), reduced the amount of TUBA1A protein and prevented incorporation of TUBA1A into microtubule polymers. Reduced Tuba1a α-tubulin in heterozygous Tuba1a ND/+ mice significantly impacted axon extension and impaired formation of forebrain commissures. Neurons with reduced Tuba1a caused by Tuba1a ND had altered microtubule dynamics and slower neuron outgrowth compared to controls. Neurons deficient in Tuba1a failed to localize microtubule associated protein-1b (Map1b) to the developing growth cone, likely impacting reception of developmental guidance cues. Overall, we show that reduced Tuba1a is sufficient to support neuronal migration, but not axon guidance, and provide mechanistic insight as to how TUBA1A tunes microtubule function to support neurodevelopment." @default.
- W3022865720 created "2020-05-13" @default.
- W3022865720 creator A5009340020 @default.
- W3022865720 creator A5024690539 @default.
- W3022865720 creator A5054614732 @default.
- W3022865720 creator A5059846654 @default.
- W3022865720 creator A5073090618 @default.
- W3022865720 date "2020-05-06" @default.
- W3022865720 modified "2023-10-16" @default.
- W3022865720 title "Tuba1a is uniquely important for axon guidance through midline commissural structures" @default.
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